title: Bioanalytical LC-MS of therapeutic oligonucleotides.
abstract: Therapeutic oligonucleotides (OGNTs) are important biopharmaceutical drugs for the future, due to their ability to selectively reduce or knockout the expression of target genes. For the development of OGNTs, reliable and relatively high-throughput bioanalytical methods are required to perform the quantitative bioanalysis of OGNTs and their metabolites in biological fluids (e.g., plasma, urine and tissue). Although immunoaffinity methods, especially ELISA, are currently widely applied for this purpose, the potential of LC-MS in OGNT analysis is under investigation. Owing to its inherent ability to monitor the individual target OGNTs as well as their metabolites, LC-MS is now evolving into the method-of-choice for the bioanalysis of OGNTs. In this paper, the state-of-the-art of bioanalytical LC-MS of OGNTs and their metabolites in biological fluids is critically reviewed and its advantages and limitations highlighted. Finally, the future perspective of bioanalytical LC-MS, that is, lower detection levels and potential generic LC-MS methodology, is discussed.
authors.affiliation: Proxy Laboratories, Archimedesweg 25, 2333 CM Leiden, The Netherlands. wdvandongen@gmail.com
authors.forename: William D
authors.initials: WD
authors.lastname: van Dongen
authors.forename: Wilfried M A
authors.initials: WM
authors.lastname: Niessen
mesh_terms: D053000:Analytic Sample Preparation Methods; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D009841:Oligonucleotides / Q000032:analysis* / Q000302:isolation & purification / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: D009841:Oligonucleotides